The lanthionine-containing antibiotic peptides, or “lantibiotics”, are a group of natural products secreted by various Gram-positive bacteria. The defining structural feature of this class of compounds is the presence of the thioether amino acids lanthionine and methyllanthionine, formed via specialised biosynthetic pathways acting on ribosomally synthesised, linear peptide precursors.
Lantibiotics have been classified into two classes, type-A and type-B. Type-A lantibiotics are generally elongate amphiphiles that retain substantial linear sections in their structure. Examples of type-A lantibiotics are nisin and subtilin. Nisin and related molecules can bind to lipid II, an indispensible intermediate in bacterial cell wall synthesis. In addition, the type-A lantibiotics are capable of forming pores in plasma membranes. The potent antimicrobial activity of the type-A lantibiotics is thought to derive from the combination of their lipid II binding and pore forming capabilities.
Type-B lantibiotics are generally smaller peptides that are folded and cross-linked into globular shapes and lack extensive linear peptide sections. Examples of type-B lantibiotics are Mersacidin, Actagardine and Cinnamycin. Like the type-A lantibiotics they have antimicrobial activity that is believed to derive mainly from their ability to bind to Lipid II, as they are not capable of forming pores in the bacterial membranes.
Mersacidin and actagardine have potent antibacterial activity against a range of Gram-positive organisms including Streptococcus, Enterococcus and Clostridium species.
For reviews, see Sahl and Bierbaum (1998) Annual Rev. Microbiol. 52:41-79; van Kraaij, de Vos, Siezen and Kuipers, Nat. Prod. Rep. 1999, 16, 575; Chatterjee, Paul, Xie and van der Donk, Chem. Rev. 2005, 105, 633.
Actagardine and analogues have been reported to be produced by two species of Actinoplanes; A. garbadinensis and A. liguriae [Parenti, Pagani, Beretta, J. Antibiotics, 1976, 29, 501; U.S. Pat. No. 6,022,851]. Actagardine is produced from a pre-pro-peptide, the C-terminal portion of which has the polypeptide sequence of SSGWVCTLTIECGTVICAC. This polypeptide is modified by the following crosslinks, creating secondary and tertiary structure: crosslink 1-6, Lanthionine (Ser-Cys); crosslink 7-12, Beta-methyllanthionine (Thr-Cys); crosslink 9-17, Beta-methyllanthionine (Thr-Cys); crosslink 14-19, Beta-methyllanthionine sulfoxide (Thr-Cys). Also co-produced is an analogue [Zimmerman, Metzger and Jung, Eur. J. Biochem 1995, 228, 786] in which the crosslink 14 and 19 is not oxidized i.e. it is a beta-methyllanthionine not betamethyllanthionine sulfoxide which is named herein deoxyactagardine.
A further variant, herein called deoxyactagardine B, derived from a propeptide with a C-terminal sequence SSGWVCTLTIECGTLVCAC and lacking a sulphoxide on the crosslink between residues 14 and 19 has also been isolated from A. liguriae (as discussed in co-pending application PCT/GB2007/000138 (WO/2007/083112), which is herein incorporated by reference).
The structures of actagardine and deoxyactagardine B are shown below.

U.S. Pat. No. 6,022,851 describes the isolation of actagardine and related forms from isolated strains of A. garbadinensis and A. liguriae. 